The symptom burden of Irritable Bowel Syndrome in tertiary care during the COVID‐19 pandemic

Abstract Background The COVID‐19 pandemic caused unprecedented disruption to healthcare services worldwide with well‐documented detrimental effects on mental health. Patients with refractory disorders of gut‐brain interaction such as Irritable Bowel Syndrome (IBS) seen in tertiary care tend to exhibit higher levels of psychological comorbidity, but the impact of the pandemic on IBS symptom severity in tertiary care is unknown. Methods As part of routine clinical care, consecutive tertiary referrals with refractory IBS patients prospectively completed a series of baseline questionnaires including IBS symptom severity score (IBS‐SSS), non‐colonic symptom score, Hospital Anxiety and Depression (HAD), and Illness impact scores. The symptom severity questionnaire data were compared for consecutive patients seen in tertiary care 12 months before and after the onset of COVID‐19 pandemic restrictions. Key Results Of 190 consecutive tertiary referrals with IBS, those seen during the pandemic had greater IBS severity (IBS‐SSS: 352 vs. 318, p = 0.03), more severe extra‐intestinal symptoms (non‐colonic score: 269 vs. 225, p = 0.03), sleep difficulties (p = 0.03), helplessness and loss of control (p = 0.02), but similar HAD‐Anxiety (p = 0.96) and HAD‐Depression (p = 0.84) scores. During the pandemic, unmarried patients (p = 0.03), and keyworkers (p = 0.0038) had greater IBS severity. Conclusions and Inferences This study has shown for the first time that patients seen in tertiary care with refractory IBS during the COVID‐19 pandemic had a significantly higher symptom burden emphasizing the importance of gut‐brain axis in IBS. Furthermore, lack of support and perceived loss of control appear to be contributory factors.


| INTRODUC TI ON
In recent years, significant advances in the understanding of Irritable Bowel Syndrome (IBS) include its reclassification as a disorder of gut-brain interaction (DGBI), 1 and the recognition of the importance of a spectrum of gastrointestinal, extra-intestinal and psychological symptom clusters in the identification of subgroups. 2 Recent data suggest that these symptom clusters have long-term prognostic significance. 3 Those with a high psychological symptom burden at baseline have higher symptom severity, are more likely to be refractory to treatments, more likely to seek consultations, 4 and are more likely to be referred to tertiary care.
The COVID-19 pandemic has caused significant disruption to healthcare services. Moreover, the impact of the subsequent lockdowns and social distancing regulations on mental health are well documented. 5 In the aftermath of the COVID-19 pandemic, much of the focus on recovery of gastroenterology services has been on restoring endoscopic activities, and services for "high-risk" chronic gastrointestinal conditions including inflammatory bowel and liver diseases. 6 Despite patients with IBS having risk factors for symptom regression via the gut-brain axis, nothing is known about the impact of the pandemic on IBS severity and the burden that this could place on healthcare resources.
The aims of this study were therefore to compare prospectively obtained data on baseline gastrointestinal, extra-intestinal and psychological symptom severities in consecutive patients with refractory IBS seen in tertiary care during the COVID-19 pandemic restrictions, with patients seen over the same time period before the onset of the pandemic.

| Patient population
As part of their routine care, consecutive patients with IBS referred to a tertiary DGBI center prospectively completed a series of baseline symptom questionnaires. All patients fulfilled clinical diagnostic criteria for IBS 7 verified by a gastroenterologist and all had failed to respond to IBS dietary and medical treatments for 12 months, and were eligible for consideration for gut-brain psychological therapies as per United Kingdom national recommendations. 7 Prior to being allocated a clinic appointment, all patients prospectively completed the following baseline questionnaires in paper form; Bristol stool chart to determine IBS-subtypes as per Rome IV crite- The IBS-SSS score allows the evaluation of the severity of abdominal pain and distension, frequency of pain, bowel habit satisfaction, and how patients perceive IBS interferes with their life on a visual analog scale of 0-100. 9 The maximum possible score is 500, with severe IBS indicated by scores of >300. This scoring system is now universally used in IBS studies and trials to measure IBS severity and assess response to therapeutic interventions.

| Non-colonic symptom score
The IBS non-colonic score assesses the severity of extra-intestinal symptoms. Patients are required to score each component using a visual analog scale of 0 to 100. 12 These components include nausea and vomiting, early satiety, headaches, backaches, lethargy, excess flatulence, heartburn, urinary symptoms, thigh pain, and muscle and joint pains. To obtain the final non-colonic score, the sum of the 10 component sub-scores is divided by two. The maximum score that can be obtained is 500, with higher scores illustrating a worse extraintestinal clinical picture. 12  • Clinical anxiety was high, and sleep disturbance, a feeling of loss of control, and isolation appeared to be contributory factors to the greater Irritable Bowel Syndrome severity seen during the pandemic.
• This study emphasizes the role of the gut-brain axis and the need for access to multidisciplinary integrated care within a biopsychosocial model for Irritable Bowel Syndrome during the recovery phase post-pandemic.
patients. 11 The questionnaire has 14 components, scored from 0 to 3, with seven relating to anxiety and seven to depression. The maximum score for either depression or anxiety is 21. Scores of below 8 are considered normal, while scores ≥8 indicate clinical depression or anxiety. 11

| Illness impact questionnaire
The illness impact score has an inverse relationship to a patient's quality life, with 15 components on a visual analog scale, scored out of 500. 12 A higher illness impact score illustrates a poorer patient quality of life. For instance, this includes evaluating feelings of irritability, inferiority or hopelessness to asking patients to rate the enjoyment of their leisure time.

| Data collection and analysis
Demographic and questionnaire data were analyzed and com- During the post-pandemic period studied, there were national or regional restrictions in place throughout the 12 months in accordance with UK national government and public health policies. This study period encompassed three national lockdowns, and at both the beginning (23/03/2020), and end of the post-pandemic study period (23/03/2021), citizens were required by law to "stay at home," with significant restrictions on non-essential gatherings, other than "keyworkers" in certain professions critical to the pandemic response (health and social care, education and childcare, key public services, local and national government, food and other necessary goods, transport, public safety and national security, and utilities, communication and financial services) citizens were all required to work from home, and non-essential travel and non-essential retail outlets remained closed. 16 The study period post-onset of the COVID-19 pandemic included a period between 23/03/2020 and 03/06/2020 when all non-emergency/non-urgent outpatient care and diagnostics including the DGBI clinic were suspended, due to redeployment of medical staff to emergency, acute care and urgent cancer referrals.
Due to the restrictions that were in place throughout the post-pandemic period, routine face-to-face clinics did not resume during the timeframe of the study. All patients that completed their pre-clinic questionnaires after resumption of the clinic therefore had their tertiary clinic appointment remotely, via video consultation. As per the DGBI clinic's normal pre-pandemic procedures, following resumption of the DGBI clinic on 03/06/2020, all patients returned pre-clinic questionnaires in paper form, via the postal system, prior to being allocated their video consultation appointment.
Questionnaire data were analyzed using descriptive statistics and pre and post-pandemic data were compared using the Chisquare and Mann-Whitney U-test where appropriate on a standard statistical software package (Stats Direct v.3.1.1, United Kingdom).
p-values ≤0.05 were considered statistically significant.

| RE SULTS
190 consecutive tertiary referrals with IBS were included, 107 patients were assessed in the 12 months prior to the pandemic, and 83 patients completed their pre-clinic questionnaires during the 12-months post-onset of COVID-19 restrictions in the UK. There were no significant differences in the demographics of the two cohorts, Table 1. Within the pandemic cohort, those with IBS who worked within keyworker occupations defined by the UK government as critical to the response to the pandemic (n = 33), had significantly greater IBS severity when compared to those that were either able to work from home, those that were retired, or unemployed (n = 50); median IBS-SSS keyworkers versus non-keyworkers: 335 vs. 278.5, u = 1,133, p = 0.0038 (95% CI: 19 to 87).

| Illness impact, anxiety and depression scores
The overall illness impact of refractory IBS on quality-of-life was similar in both groups, but sleep disturbance (p = 0.03), helplessness and loss of control feelings (p = 0.02) were significantly higher in those seen during the pandemic (Table 4)

| DISCUSS ION
This study is the first to demonstrate changes in the symptom profiles and severity of IBS referrals to tertiary care during the These findings are unlikely to be by chance as the pre-pandemic data in our study on gastrointestinal, extra-intestinal, and psychological symptom scores (Table 2), are almost identical to published baseline data using the same questionnaires from almost 1,500 patients with refractory IBS from our unit which have been stable over the past 10 years. 10,14,15 Moreover, the observed reciprocal relationship between higher perceived abdominal distension severity and abdominal pain severities in the pandemic group is consistent with the recent literature on IBS symptom severity. 18 The patients in this tertiary, refractory, population had high levels of psychological comorbidity with the majority of patients in both the pre-pandemic and pandemic cohorts having clinical levels of anxiety. It was interesting to note that there was little difference in the anxiety and depression scores between the two groups before and during the pandemic, especially with regard to anxiety. Similar to our findings in a population of tertiary patients with IBS who had high levels of anxiety and depression even in the pre-pandemic group, longitudinal studies that have followed up patients who had pre-existing high levels of anxiety and depression pre-pandemic have found minimal changes in the symptom severity levels of anxiety and depression during the COVID-19 pandemic. 19,20 This therefore suggests that other psychological factors, beyond anxiety and depression, relating to their response to the pandemic might be driving their symptom deterioration. The effects of stress on the gut-brain axis and how this contributes to symptoms in DGBI is well recognized. Recent evidence suggests that stress has resulted in an increase in the prevalence of IBS during the COVID-19 pandemic. 21 Moreover, patients with IBS and high levels of anxiety, such as those included in our study are more likely to be susceptible to severe exacerbations due to aberrant coping strategies [22][23][24][25] and lower levels TA B L E 1 Demographics of tertiary referrals with IBS seen 12 months before compared with those seen during the COVID-19 pandemic loss of control and helplessness as well as sleep disturbance among those within the pandemic cohort in our study. While the exact reasons for more sleep disturbance in the pandemic group is unclear, social support during the pandemic restrictions may be a contributory factor. During the COVID-19 pandemic there is evidence that lower levels of social support were associated with higher risk of sleep disturbance and psychological effects. 28 Interestingly, our data also suggest that social support may be a protective factor. Those that were unmarried had higher IBS symptom severity. Social isolation, which has been shown to be associated with gastrointestinal symptoms and related psychological distress during the pandemic, 29 is a possible explanation, although unfortunately it was not possible to draw firm conclusions on this retrospectively, due to the lack of data available on whether or not those who were unmarried, lived alone.
During the pandemic, occupation also appeared to be an important factor associated with IBS symptom severity. Compared to keyworkers who were critical for the response to the pandemic, those that could stay at home (non-keyworkers, unemployed and retired) had  In conclusion, patients seen in tertiary care with IBS during the pandemic had a significantly higher symptom burden emphasizing the importance of gut-brain axis in IBS. Furthermore, lack of support and perceived loss of control appear to be contributory factors. These observations suggest that investment and provision of integrated multidisciplinary IBS care within a biopsychosocial model should not be ignored when planning the recovery of gastroenterology services.

CO N FLI C T O F I NTE R E S T
None of the authors have any relevant conflicts of interests to declare.

TA B L E 4
Comparison of median IBS illness impact scores in tertiary referrals with IBS 12 months before and during the COVID-19 pandemic (*p ≤ 0.05)